Kemal Sagduyu

Antidepressant-associated chronic irritable dysphoria (ACID) in STEP-BD patients

BACKGROUND It has been proposed that antidepressants can induce a chronic, dysphoric, irritable state in bipolar patients (called ACID for antidepressant-associated chronic irritable dysphoria). This phenomenon has only been described in case series format, and has not been prospectively validated. METHODS Prospective data from the first 1500 patients (62.7% with bipolar I, 30.1% with bipolar II, and 7.2% with NOS) treated in the STEP-BD database were examined and those who were euthymic for at least one month at study entry, subsequently developed a depressive episode, and were then followed for one year were identified. Outcome of those who received an antidepressant for this depressive episode (n=27) was compared to those who did not (n=56), with particular attention given to the presence of the proposed symptom triad of ACID, namely dysphoria, irritability, and middle insomnia. RESULTS Patients treated with antidepressants were ten times more likely to develop ACID than those who were not (Hazard ratio=9.95, CI=1.103-89.717, P=0.04). However, the hazard ratio dropped to 1.05 (P=0.99) when corrected for significant covariates, notably past antidepressant-related manic switch and sex. DISCUSSION This study does not support the existence of ACID as an independent phenomenon. Rather, ACID appears to be part of a broader spectrum of antidepressant treatment-emergent affective switches.

Relationship among latitude, climate, season and self-reported mood in bipolar disorder

OBJECTIVE Many researchers have analyzed seasonal variation in hospital admissions for bipolar disorder with inconsistent results. We investigated if a seasonal pattern was present in daily self-reported daily mood ratings from patients living in five climate zones in the northern and southern hemispheres. We also investigated the influence of latitude and seasonal climate variables on mood. METHOD 360 patients who were receiving treatment as usual recorded mood daily (59,422 total days of data). Both the percentage of days depressed and hypomanic/manic, and the episodes of depression and mania were determined. The observations were provided by patients from different geographic locations in North and South America, Europe and Australia. These data were analyzed for seasonality by climate zone using both a sinusoidal regression and the Gini index. Additionally, the influence of latitude and climate variables on mood was estimated using generalized linear models for each season and month. RESULTS No seasonality was found in any climate zone by either method. In spite of vastly different weather, neither latitude nor climate variables were associated with mood by season or month. CONCLUSION Daily self-reported mood ratings of most patients with bipolar disorder did not show a seasonal pattern. Neither climate nor latitude has a primary influence on the daily mood changes of most patients receiving medication for bipolar disorder.

Impact Of Sunlight on the Age Of Onset Of Bipolar Disorder

Bauer M, Glenn T, Alda M, Andreassen OA, Ardau R, Bellivier F, Berk M, Bjella TD, Bossini L, Del Zompo M, Dodd S, Fagiolini A, Frye MA, Gonzalez‐Pinto A, Henry C, Kapczinski F, Kliwicki S, König B, Kunz M, Lafer B, Lopez‐Jaramillo C, Manchia M, Marsh W, Martinez‐Cengotitabengoa M, Melle I, Morken G, Munoz R, Nery FG, O’Donovan C, Pfennig A, Quiroz D, Rasgon N, Reif A, Rybakowski J, Sagduyu K, Simhandl C, Torrent C, Vieta E, Zetin M, Whybrow PC. Impact of sunlight on the age of onset of bipolar disorder. Bipolar Disord 2012: 14: 654–663.

Relationship between sunlight and the age of onset of bipolar disorder: an international multisite study.

BACKGROUND The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. METHODS Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. RESULTS There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. LIMITATIONS Recall bias for onset and family history data. CONCLUSIONS A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.

Association between age of onset and mood in bipolar disorder: comparison of subgroups identified by cluster analysis and clinical observation.

BACKGROUND This study compared subgroups identified by cluster analysis and clinical observation by evaluating the association between the age of onset of bipolar disorder and self-reported daily mood ratings. METHODS Two hundred and seventy patients with bipolar disorder provided daily self-reported mood ratings for about 6 months returning 55,188 days of data. The age of onset subgroups were determined both using previously defined cutoff values based upon clinical observation (≤12 years, 13-19 years, 20-29 years, >29 years), and model-based cluster analysis. Demographic characteristics were compared in the age of onset subgroups. Univariate general linear models with age of onset subgroups and other demographic variables as fixed factors and covariates were used to analyze the percent of days depressed, euthymic and hypomanic/manic. RESULTS Using the predetermined subgroups, demographic differences were found between the four subgroups in the diagnosis of bipolar I/II, years of illness, age and use of lamotrigine. Post-hoc pairwise comparison found that patients with an age of onset less ≤ 12 years spent more days hypomanic/manic: 16.4 percent versus 8.0 for patients with an age of onset between 13 and 19 years (p=0.006) and 8.2 percent for patients with an age of onset between 20 and 29 years (p = 0.031). The majority of the additional days of hypomania/mania occurred outside of an episode. Model-based cluster analysis found a mixture of 2 distributions of onset with peaks at age 15.1 years (SD = 4.7) and 27.5 years (SD = 10.2). Analysis of these two subgroups detected no significant differences in demographic characteristics or mood ratings. CONCLUSION Age of onset subgroups arising from clinical observation may be more useful than those determined by cluster analysis.

Comparison of sleep/wake parameters for self-monitoring bipolar disorder

BACKGROUND Psychosocial interventions may teach patients with bipolar disorder to successfully detect warning signs of relapse. These interventions often include ongoing self-monitoring of sleep. We previously reported that a change in sleep duration (sleep plus bedrest) of >3 h may indicate that a mood change is imminent. This analysis further investigated whether sleep duration, sleep onset or sleep offset was the most useful sleep/wake parameter to monitor for an oncoming mood change. METHODS 101 adult outpatients receiving treatment as usual recorded mood, sleep and medications every day on a home computer for a mean of 265+/-103 days. A daily time series of mood, sleep duration (sleep plus bedrest), sleep onset and sleep offset was constructed for each patient. After applying an ARIMA (0,1,1) filter, a cross correlation function was used to analyze the temporal relationship between the residuals for lags of +/-7 days. RESULTS Less frequent significant correlations were found between a change in either sleep onset or sleep offset and mood, than between sleep duration and mood. Patients with a significant correlation between sleep duration and mood included 86% of those with a significant correlation between sleep onset or sleep offset and mood. Mean sleep duration when euthymic was long (> or =8 h in 89% of patients, > or =9 h in 51% of patients). LIMITATIONS Self-reported data, naturalistic study, and computer access required. CONCLUSIONS Self-monitoring of sleep duration is recommended for patients with bipolar disorder. Better understanding of the long sleep duration of euthymic patients is required.

Influence of light exposure during early life on the age of onset of bipolar disorder

BACKGROUND Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. METHODS Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4 N and 70.7 N, and 1.2 S and 41.3 S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation. RESULTS More hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. CONCLUSIONS Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life.

Drug treatment patterns in bipolar disorder: analysis of long-term self-reported data

BackgroundThe objective of this study is to investigate drug treatment patterns in bipolar disorder using daily data from patients who received treatment as usual.MethodsPatients self-reported the drugs taken daily for about 6 months. Daily drug use and drug combinations were determined for each patient, both by the specific drugs and by medication class. The drug load was calculated for all drugs taken within a medication class.Results and discussionFour hundred fifty patients returned a total of 99,895 days of data (mean 222.0 days). The most frequently taken drugs were mood stabilizers. Of the 450 patients, 353 (78.4%) took a stable drug combination for ≥50% of days. The majority of patients were taking polypharmacy, including 75% of those with a stable combination. Only a small number of drugs were commonly taken within each medication class, but there were a large number of unique drug combinations: 52 by medication class and 231 by specific drugs. Eighty percent of patients with a stable combination were taking three or less drugs daily. Patients without a stable combination took drugs but made frequent changes. Taking more than one drug within a medication class greatly increased the drug load.To summarize, (1) patients were more likely to take a mood stabilizer than any other drug; (2) although most patients were taking polypharmacy, there were no predominant drug regimens even among those taking a stable combination; and (3) most patients with a stable combination take a relatively small number of drugs daily. The wide variation in drug regimens and numerous possible drug combinations suggest that more evidence is needed to optimize treatment of bipolar disorder.

The association between concurrent psychotropic medications and self-reported adherence with taking a mood stabilizer in bipolar disorder

Multiple psychotropic medications are routinely prescribed to treat bipolar disorder, creating complex medication regimens. This study investigated whether the daily number of psychotropic medications or the daily number of pills were associated with self‐reported adherence with taking a mood stabilizer.

A cross-over, post-electroconvulsive therapy comparison of clinical recovery from rocuronium versus succinylcholine

STUDY OBJECTIVE To evaluate the effect of the neuromuscular blocking agent, rocuronium, on clinical recovery from electroconvulsive therapy (ECT) as compared with succinylcholine. DESIGN Cross-over study. SETTING University hospital. PATIENTS 13 ASA physical status I and II patients, ages 18 to 60 years, receiving ECT three times a week. INTERVENTIONS Each patient received either succinylcholine before the first ECT session (Group S) and rocuronium before the third ECT session (Group R). Muscle paralysis was produced with succinylcholine one mg kg(-1) intravenously (IV) or rocuronium 0.3 mg kg(-1) IV. Reversal of the residual neuromuscular block (Group R) was accomplished with 10 microg kg(-1)of atropine and 20 microg kg(-1)of neostigmine after completion of the ECT procedure. MEASUREMENTS Motor seizure duration time, time to first spontaneous breathing, eye opening, head lift, and tongue depressor test were recorded. MAIN RESULT Motor seizure duration and time to first spontaneous breath was longer (33.6 sec vs. 24.2 sec; 9.46 min vs 8.07 min, respectively) in the rocuronium group than the succinylcholine group. No significant difference was detected between the two groups in eye opening, head lift, or tongue depressor testing. CONCLUSION Rocuronium, when used in conjunction with a reversal agent, may be an adequate alternative to succinylcholine as a neuromuscular blocker during ECT.